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Celiac Disease, Refractory

A small intestinal mucosa from a case of refractory coeliac disease immunostained sequentially for CD3 (alkaline phosphatase-blue) and CD8 (peroxidase-brown). Most intraepithelial lymphocytes are CD3+, CD8-.Courtesy pubcan.org
Mucosa  in refractory celiac  disease immunostained sequentially for CD3 (alkaline phosphatase-blue) and CD8 (peroxidase-brown). Most intraepithelial lymphocytes are CD3+, CD8-. Courtesy pubcan.org

What Is Refractory Celiac Disease?

[dropcap]R[/dropcap]efractory celiac disease, formerly called refractory sprue, is a severe complication characterized by persistence of symptoms and intestinal inflammation despite gluten free diet after 12 months.1

Refractory celiac disease appears in two forms, ulcerative jejunitis (RCD I) and cryptic intestinal T-cell lymphoma (RCD II).

Patients with RCD I seem to profit from immunosuppressive treatment, but positive response to corticosteroid treatment does not exclude underlying enteropathy–associated T-cell lymphoma (EATL).

Patients with RCD II have a high percentage of abberant T-cells and is usually resistant to medical therapies. The presence of an aberrant clonal intraepithelial T-cell population has led to the designation of refractory celiac disease with this population as a cryptic intestinal T-cell lymphoma, characterized by frequent dissemination to the blood and the entire gastrointestinal lining.2

  • Refractory sprue may occur after an initial response to gluten free diet or without any evidence of preexisting celiac disease. All other causes of malabsorption must be excluded, such as collagenous colitis.
  • In a subgroup of patients with enteropathy-associated T-cell lymphoma (EATL) there is progressive deterioration of a refractory form of celiac disease. The prognosis is poor, although some patients respond to corticosteroids and immunosuppressive agents.3
  • A nationwide Finnish study showed that patients of male gender, older age, severe symptoms or seronegativity (negative antibody result) at the diagnosis of celiac disease are at risk of future refractory coeliac disease and should be followed up carefully.4
  • Chorea has been described as a paraneoplastic phenomenon in patients with non-Hodgkin’s lymphoma and has been described as associated with lymphoma arising from a background of refractory celiac disease. The finding of chorea in association with celiac disease should prompt a search for possible underlying intestinal T-cell lymphoma.5

How Prevalent Is Refractory Celiac Disease?

Sources:
  1. Murray JA, The widening spectrum of celiac disease. American Journal of Clinical Nutrition. Mar 1999;69 (3):354-365. [↩]
  2. Culliford AN, Green PH. Refractory sprue. Current Gastroenterology Reports. Oct 2003;5(5):373-8. [↩]
  3. Culliford AN, Green PH. Refractory sprue. Current Gastroenterology Reports. Oct 2003;5(5):373-8. [↩]
  4. Ilus T, Kaukinen K, Virta LJ, Huhtala H, Mäki M, Kurppa K, Heikkinen M, Heikura M, Hirsi E, Jantunen K, Moilanen V, Nielsen C, Puhto M, Pölkki H, Vihriälä I, Collin P. Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease. Aliment Pharmacol Ther. 2014 Feb;39(4):418-25. doi: 10.1111/apt.12606. [↩]
  5. Kitiyakara T, Jackson M, Gorard DA. Refractory coeliac disease, small-bowel lymphoma and chorea. J R Soc Med. 2002 Mar;95(3):133-4. [↩]

Lymphomas, Extraintestinal

Lymph System. National Cancer Institute.What Are Extraintestinal Lymphomas?

[dropcap]E[/dropcap]xtraintestinal lymphomas (non-Hodgkin’s) are malignancies that arise in peripheral lymphatic tissue outside the intestinal tract from B-cell and T-cell lymphocytes.

Q: What is peripheral lymphatic tissue?

A: Peripheral lymphatic tissue includes lymph vessels, lymph, lymph nodes, and lymphocytes.

Lymph vessels branch into all the tissues of the body, carrying lymph, a clear fluid that contains white blood cells, especially B-cell and T-cell lymphocytes.

Lymph vessels are connected to lymph nodes which are small, round masses of tissue that store white blood cells. They also trap and remove bacteria or other harmful substances that may be in the lymph. Groups of lymph nodes are found in the neck, underarms, chest, abdomen, and groin.

Ninety percent (90%) of extraintestinal lymphomas are B-cell type and ten percent (10%) are T-cell type. In this malignancy, lymph nodes are replaced by cancer cells. Some are more aggressive than others.

In 2010, there were an estimated 509,065 people living with non-Hodgkin lymphoma in the United States according to the National Cancer Institute.

What Are Extraintestinal Lymphomas In Celiac Disease and/or Gluten Sensitivity?

Cancer, Post-Cricoid

Anatomy of Upper Airway and Throat. Courtesy Wikipedia.org
Anatomy of Upper Airway and Throat. Courtesy Wikipedia.org

What Is Post-Cricoid Carcinoma?

[dropcap]P[/dropcap]ost-cricoid carcinoma is a rare malignancy arising in the hypopharynx.

Q: What is the hypopharynx?

A: The hypopharynx is the lower portion of the pharynx that opens into the larynx. It is comprised of the postcricoid region, pyriform sinus, and posterior hypopharyngeal wall.

Tumors rarely appear in the posterior pharyngeal wall or postcricoid region without also involving the pyriform sinus. The lack of anatomic barriers between these sites and a propensity for these tumors to develop in the pyriform sinus and spread outward account for this phenomenon.

Overall prognosis for these tumors is poor. Because of the rich organic lymphatic and vascular networks, aggressive growth and early cervical metastases (compared with cancers at other head and neck sites) characterize these cancers.

A study investigating the clinical course of 21 patients with post-cricoid carcinoma found the 5-year cause-specific survival rate was 52%. All the patients who eventually died did so within 3 years of the treatment. Seven patients had distant metastases, representing a higher frequency as compared with that of patients with recurrence of the primary focus and cervical lymph node metastasis. All of these patients who had been treated by surgery died of the cancer.1

Unfortunately, hypopharyngeal cancers are discovered at a later stage than other head and neck cancers. The delay in diagnosis from symptom onset averages 10 months.2

What Is Post-Cricoid Carcinoma In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Asakage T, Nakao K, Ebihara Y, Fujishiro Y, Watanabe K. A clinical study of post-cricoid carcinoma. Acta Otolaryngol Suppl. 2007 Dec;(559):118-22. doi: 10.1080/03655230701599354. [↩]
  2. http://emedicine.medscape.com/article/848359-overview [↩]

Cancer Of The Esophagus 

A real photomicrograph of carcinoma of the esophagus. Panorama of 6 photos of a slide at 40x through the microscope. Some areas may appear blurry due to shallow DOF.
A real photomicrograph of carcinoma of the esophagus. Panorama of 6 photos of a slide at 40x through the microscope. Some areas may appear blurry due to shallow DOF.

What Is Cancer Of The Esophagus?

[dropcap]C[/dropcap]ancer of the esophagus is a malignancy arising in the stratified squamous cell lining of any part of the esophagus and having a poor prognosis.

This tumor first invades the deeper layers of the esophagus which includes the layer beneath the mucosa (submucosa) and muscle before it may invade structures close to it including the aorta and trachea. Later, it may spread to organs further away such as the liver, lungs and bones.

Q: What is the stratified squamous cell lining of the esophagus?

A: Stratified squamous cells are flat epithelial cells that are composed of several layers, called the epithelium. This type of epithelium forms the surface mucosa that lines the inside of the esophagus.

The esophagus itself is a muscular tube that transports swallowed substances to the stomach. It begins at the cricoid cartilage (Adam’s apple) as a continuation of the pharynx in the throat and ends at the lower esophageal sphincter (LES).

The LES is a circular muscle surrounding the junction of the esophagus and stomach. The LES opens to allow swallowed food and liquids to enter the stomach and closes to prevent their travelling back into the esophagus.

Who is Affected in the General Population?

Esophageal cancer is the fifth leading cause of death in men from cancer worldwide.1

What Is Cancer Of The Esophagus In Celiac Disease and/or Gluten Sensitivity?

Sources:
  1. Feldman M, Friedman LS, Brandt LJ. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease. ed 9. Philadelphia: Saunders; 2010. pp. 745–767. [↩]

Atherosclerosis

ahterosclerosis celiac disease complication symtpomWhat Is Atherosclerosis?

[dropcap]A[/dropcap]therosclerosis is a disease of arteries involving the buildup of fatty material called plaque along the walls of medium and large arteries characterized by patchy subintimal thickening, hardening, and loss of elasticity of blood vessels.

The intima is the innermost layer of an artery, having contact with blood. The subintima is beneath it.

Q: What happens when arteries become narrowed and less flexible?

A: Narrowing of the inside diameter of blood vessels and hardening of their walls reduce or obstruct blood flow through them which impairs their ability to supply tissues of the body with oxygen and nourishment.

When tissues are deprived of oxygen, pain and dysfunction results such as angina pectoris involving heart muscle because the heart continually needs oxygen never being able to rest.

It is thought that atherosclerosis develops from 1) epithelial cell dysfunction of the intima, and 2) lipid (fat) accumulation in smooth muscle cells and in foam cells, causing buildup of fatty deposits on the inside walls progressing to fibrous plaque formation. That is, intimal smooth muscle cells are surrounded by connective tissue and intracellular and extracellular lipids (fat build-up inside and outside of these cells).

What Is Atherosclerosis In Celiac Disease and/or Gluten Sensitivity?